Streptokinase is effective to dissolve various types of blood clots both within and outside of the body. However, a number of difficulties are encountered in the use of the enzyme in therapeutic treatment. Antibodies against streptokinase are present in the blood of essentially all human beings but the antibody level or "titer" varies widely among individuals. In order for treatment with streptokinase to be effective, the blood of each patient must be titrated to determine the proper initial dose of enzyme sufficient to nullify the antibodies present in the blood and to provide the proper level of streptokinase enzyme to function as desired, while avoiding the deleterious effects of an excessive dose of streptokinase.
Further, during treatment, the patient develops an increased concentration of antibodies to the enzyme. Hence, a subsequent treatment with streptokinase at a later date may require an increased streptokinase dosage. Also, a subsequent dose may be dangerous since the patient can become "sensitized" to the enzyme, and may thus undergo a severe allergic reaction.
Additionally, doses of the enzyme must be adequate in the first place in order to effectively dissolve blood clots, and they must be administered repeatedly or continuously, generally by intravenous drip, since the enzyme is metabolized by the body in a relatively short period of time.
Accordingly, there is a need for a substrate having a streptokinase-like activity, yet which has increased stability in the body and which also is less subject to neutralization by the antibodies present in the blood stream to make possible a reduction in the amount and frequency of the dosage. Along with such reduced dosages, the danger of allergic reaction and other side effects is reduced.